The present invention is directed to a novel composition of matter for the sustained release of a therapeutic agent. More specifically, the present invention relates to a composition for the sustained release of a biologically active therapeutic agent from a biodegradable, amorphous carbohydrate glass matrix. Upon administration to a mammal, the amorphous carbohydrate glass matrix slowly dissolves, releasing the biologically active therapeutic agent into the physiological fluids of the animal.
The preparation and employment of amorphous carbohydrate glasses are known in the "candy industry" as well as in the production of medicated lozenges. However, amorphous carbohydrate glasses have not been employed as matrix material for sustained release polypeptide compositions. Various sustained release methods and compositions are known for administering therapeutic agents to both humans and animals alike. U.S. Pat. No. 4,671,953, issued to Stanley et al. in 1987, describes a method and composition for administering sedatives, analgesics and anesthetics to a patient by incorporating the therapeutic agent into a lollipop. The lollipop is composed of a carbohydrate matrix or "candy matrix" with the therapeutic agent dispersed throughout the matrix. As the patient licks or sucks on the "candy matrix" the matrix breaks down, releasing the drug into the oral cavity where the drug is absorbed across the mucosal cavity. A serious limitation to this method of administering a therapeutic agent to a patient is that the therapeutic agent must be sufficiently lipophilic that it will readily pass across a mucosal membrane. Examples of therapeutic agents which can be administered by this method include morphine, fentanyl, valium, midazolam and the like. Polypeptides are not sufficiently lipophilic such that they could be administered to a patient by this means.
U.S. Pat. No. 4,765,980, issued to DePrince et al. in 1988, describes a method for stabilizing porcine growth hormone with porcine serum albumin in sustained release implant devices for swine. The porcine growth hormone and stabilizing amount of porcine serum albumin are compressed into a tablet or pellet with binders such as sodium bentonite, ethyl cellulose, stearic acid, adipic acid, fumaric acid, polyethylene glycol, deacetylated chitin and cellulose acetate. The pellets or tablets are loaded in a reservoir which can be implanted subcutaneously in swine where the growth hormone is slowly released from the reservoir. Typically, the matrix material of the reservoir is composed of polyalkylenes, polycarbonates, polyamides, modacrylic copolymers, polyesters and the like.
U.S. Pat. No. 4,857,506, issued to Tyle in 1989, describes sustained release compositions of growth hormones in multiple water-in-oil-in-water emulsions. The compositions are administered subcutaneously to an animal where the growth hormone is slowly released from the emulsion to increase the weight gain of the animal and increase milk production by a lactating animal.
U.S. Pat. No. 4,293,539, issued to Ludwig et al. in 1981, describes controlled release formulations useful in the prolonged treatment and control of microbial infections in animals. The antimicrobial agent is dispersed throughout a matrix composed of a copolymer of lactic acid and glycolic acid. The copolymeric material is polymerized without a catalyst to ensure total degradation without leaving any toxic residues. The copolymer material then is dissolved in an organic solvent and mixed with a suitable antimicrobial agent. The mixture is extruded into a desired shape and then cooled to form a hard glass-like device. Antimicrobials typically employed include penicillins, cephalosporins, tetracyclines, sulfa drugs, macrolide antibiotics and aminoglycosides.
U.S. Pat. No. 2,918,411, issued to Hill in 1959, describes a controlled release oral pharmaceutical dosage form. The essential components of the formulation include polyvinylpyrrolidone, a substantially water-insoluble agent, such as a saturated fatty acid, a saturated fatty acid ester and a pharmacologically acceptable sterol, and a pharmacologically active material. After the essential components of the formulation are mixed, the formulation is pelletized. The pellets then can be encapsulated or embodied in another type of dosage form or administered directly to a patient from the bulk pellet. Suitable pharmacologically active agents which can be employed in this sustained release composition include antibiotics, hypnotics, tranquilizing agents, antihistamines and narcotics.
Although there are a variety of sustained release compositions for many biologically active agents, there is still a need for a sustained release composition which completely degrades in the physiological fluids of the host leaving behind little, if any, residual material and which does not substantially interact with the therapeutic agent.